A Phase 1a Multicenter, Open-label Safety, Tolerability and Pharmacokinetic Study of CC-90003, a Selective Extracellular Signal-Regulated Kinase (ERK) Inhibitor, in Subjects With Locally-Advanced or Metastatic, Relapsed, or Refractory BRAF or RAS-Mutated Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Celgene
- 入组人数
- 19
- 试验地点
- 5
- 主要终点
- Pharmacokinetics (PK) observed maximum concentration (Cmax)
研究概览
简要总结
The CC-90003-ST -001 trial is a first-in-man, open-label study in subjects with locally-advanced or wide spread cancers to determine if CC-90003 (an oral medication) can be adequately tolerated with minimal side effects.
详细描述
CC-90003-ST -001 is an open-label, multicenter, Phase 1a study in subjects with locally-advanced or metastatic, solid tumors who are intolerant of, resistant to, or have relapsed after at least one line of therapy and for whom no standard therapy exists. The study will be conducted in two parts: Dose Escalation (Part 1) and Cohort Expansion (Part 2). Subjects may continue CC-90003 until progression of their underlying malignancy, the occurrence of intolerable toxicity, or physician/subject decision to discontinue CC-90003. In Part 1, cohorts of subjects with relapsed or refractory solid tumors will receive increasing doses of CC-90003 in order to assess its safety and tolerability, the maximum tolerated dose (MTD), and PK profile. In Part 2, cohorts of subjects with specific tumors that harbor mutations involving the Mitogen -Activated Protein Kinase (MAPK) pathway will receive CC-90003 at or below the MTD until progression of disease, intolerable toxicity, or physician/subject decision to discontinue CC-90003.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eligible study subjects in Part 1 and Part 2 must be 18 years or older
- •Eligible study subjects must have histologic or cytologic confirmation of advanced, unresectable or metastatic solid tumors, and have at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
- •Eligible study subjects must have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
- •Eligible study subjects must exhibit acceptable liver, bone marrow, renal and cardiac functions as assessed by laboratory tests, ECG and ECHO or MUGA scan.
排除标准
- •Subjects with symptomatic or unstable CNS metastases
- •Subjects with a history of recent (within 28 days) systemic therapy for their underlying malignancy
- •Subjects who have had surgery/radiotherapy within 2 weeks prior to start of study
研究组 & 干预措施
Dose Level 1 CC-90003
CC-90003 by mouth (PO) daily on days 1 -21 of every 28 day cycle; Cycle 1, Days 1 to 28 will constitute the dose limiting toxicity (DLT) assessment period for purposes of non-tolerated dose (NTD) and Maximum Tolerated Dose determination.
干预措施: CC-90003 (Drug)
结局指标
主要结局
Pharmacokinetics (PK) observed maximum concentration (Cmax)
时间窗: Cycle 1, Day 1, 2, 3 (predose), 8, 11 (predose), 15, 16, , Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
The maximally observed plasma concentration of CC-90003 (Cmax)
PK-Area under the plasma concentration time curve (AUC)
时间窗: Cycle 1, Day 1, 2, 3, (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
Area under the plasma concentration -time curve of CC-90003
Summary of the adverse events (type, severity, and incidence) related to CC-
时间窗: Up to 36 months
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values regardless of etiology.
Maximum Tolerated Dose (MTD) of CC-90003
时间窗: Up to 36 months
The MTD is defined as the highest dose level at which no more than 1 in 6 participants experiences a dose- limiting toxicity (DLT) during the first 28 day cycle of treatment
PK-Time to maximal plasma concentration (Tmax)
时间窗: Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
The time to reach Cmax
PK- Apparent Total Volume of Distribution (Vz/F)
时间窗: Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15,16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
PK- Apparent Total Volume of Distribution (Vz/F) During the terminal phase for CC- 90003
Accumulation index of CC-90003
时间窗: Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
Accumulation represents the relationship between the dosing interval and the rate of elimination for the drug
Dose Limiting Toxicities of CC-90003
时间窗: Up to 18 months
Number of participants with dose limiting toxicities during the Dose Escalation Phase
PK- terminal half-life; t1/2
时间窗: Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
Terminal phase elimination half-life (t1/2) is calculated as follows: t1/2 =ln(2)/λz, where λz is the first order rate constant associated with the terminal portion of the CC-90003 plasma concentration curve
PK-Apparent total body clearance (CL/F)
时间窗: Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose) 15, 16, , Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
The apparent total body clearance of CC-90003 from plasma
次要结局
- Progression Free Survival(Up to 36 months)
- Overall Survival(Up to 36 months)
- Response Rate based on RECIST 1.1(Up to 36 months)
- Duration of Response(Up to 36 months)
- Disease Control(Up to 36 Months)